Fragmentation Dynamics of Drug Bioconjugates: Insights from Mass Spectrometry (Article Review)

الملخص

Background: Anthracyclines are chemotherapeutic medications with a broad therapeutic range. They were discovered in a pigment-producing strain of Streptomyces and are generally used as an anti-cancer medication. Doxorubicin (Dox), Daunorubicin (Dau), and epirubicin (Epi), the three most important anthracyclines, used in cancer treatment as a key class of chemotherapeutic medications and are recognized as some of the most potent antineoplastics available today. Daunorubicin is a commonly prescribed anti-cancer drug used to treat various types of leukemia. This anti-cancer molecule is frequently coupled to Gonadotropin-Releasing Hormone type III  derivatives via an oxime bond, with the Serine in the fourth position substituted for Lysine (acetylated ). This conjugation not only maximizes selectivity but also minimizes systemic toxicity

Materials and Methods: These bioconjugates were found to be highly selective and significantly slowed tumor development in a wide variety of tumor types. Due to their complex architectures, these peptide-drug conjugates are often confirmed using Mass Spectrometry, which may also be utilized for analytical characterization. Soft ionization technologies such as Electrospray Ionization and Matrix-Assisted Laser Desorption/Ionizationare often used to produce protonated molecules from proteins and peptides

Results: Conversely, the mass spectra of bioconjugates with daunomycin "undergo extensive fragmentation" under conventional spectrometric conditions. Daunomycin almost always produces a specific pattern of fragmentation ions. Aglycone- or daunosamine-mediated glycosidic bond breakage is a primary mechanism for fragmentation.

Conclusion: Peptide–drug conjugates (PDCs) are prodrugs in which drug molecules are covalently linked to peptides through specific linkers. The mass spectrometric analysis of daunorubicin-containing conjugates is challenging due to the loss of the sugar moiety during ionization, and their fragmentation patterns depend on technical factors such as instrument settings, solvent composition, and the structural nature of the conjugate. A novel daunorubicin–peptide conjugate offers a safe and effective cancer therapy, and elucidating its structure requires the use of complementary MS detection techniques. Ion activation remains a key concept in the analysis of peptides, proteins, and their complexes, as ionization and fragmentation methods determine fragment patterns and support the characterization of structural features and modifications.